The following Compound (1):
is known as a selective and potent inhibitor of the HCV NS3 serine protease. Compound (1) falls within the scope of the acyclic peptide series of HCV inhibitors disclosed in U.S. Pat. Nos. 6,323,180, 7,514,557 and 7,585,845. Compound (1) is disclosed specifically as Compound #1055 in U.S. Pat. No. 7,585,845, and as Compound #1008 in U.S. Pat. No. 7,514,557. Compound (1) can be prepared according to the general procedures found in the above-cited references, which are herein incorporated by reference.
Compound (1) may also be known by the following alternate depiction of its chemical structure, which is equivalent to the above-described structure:
wherein B is
L0 is MeO—; L1 is Br; and R2 is

When synthesized according to the general procedures set forth in the above-cited references, Compound (1) is prepared as an amorphous solid which is a form that is to generally less suitable for full-scale pharmaceutical processing. Thus, there is a need to produce Compound (1) in a crystalline form to enable formulations to meet exacting pharmaceutical requirements and specifications. Furthermore, the process by which Compound (1) is produced needs to be one which is amenable to large-scale production. Additionally, it is desirable that the product should be in a form that is readily filterable and easily dried. Finally, it is economically desirable that the product be stable for extended periods of time without the need for specialized storage conditions.
U.S. patent application Ser. No. 12/559,927, filed Sep. 15, 2009, discloses the Type A crystalline form of Compound (I) and a crystalline sodium salt form of Compound (I) with more favorable pharmaceutical properties compared to the amorphous compound. However, the crystalline sodium salt is a variable hydrate which may impose challenges in production, e.g. challenges in consistent formulation characterization, manufacturing (e.g. difficulty drying) and handling. Salts with superior properties compared to the Type A crystalline form of Compound (I) and the crystalline sodium salt, e.g. a non-solvated crystalline form, would be preferred for large scale production and pharmaceutical formulation.